Process of preparing cyanine dyes with strong organic bases



Patented Feb. 6, 1940 1 UNITED STATES PROCESS OF PREPARING CYANINE ,nyiis s wrrn STRONG ORGANIC BASES Leslie George Scott Brooker, Rochester, N. Y., as- 1 signpr, by mesne assignments,- to. Eastman Kodak Company, Rochester, N. Y., a corpora-'- tion of New Jersey No Drawing.- Application January 16,1933} v -SerialNo. 651,870 e It is well known that a number'of cyanine dye condensations'are brought about by using basic media or else by the use of inorganic ale kalies.

15. For instance, dyes of what is'knownas the b-cyanine type have been prepared by the action of caustic potash, in absolute ethyl alcoholic soi lution, on a suitableinixture ofalkyl quaternary salts of heterocyclic' bases; 1928, 206.)

Again, dyes of the carbocyanine series have been prepared by the use of pyridine as a basic solvent, part of the'function of this solvent being to combine with the elements ofacid :splitoff 1. during the condensation. (of. Hamer J. 'C. S.

1 '(cf. Hamer J. 0.. S.

Again, dyes of what has beencalled the tric'arbocyanine series have been prepared by the action" of sodium alcoholate on a mixture'of'a quaternary salt and dinitro phenyl pyridinium jchloride (B. P, 351, 555) or on a mixture of glutaconic alde-' hyde dianilide hydrochloride and appropriate quaternary salt (B.P. 354,826). r

It is an object of this in'venti onto provide a process for effecting various condensations in the preparation of dyes by the use of strong or-- ganic bases, such as 'piperidine, diethylamine, triethylamine, or the like. One advantage'of this process is that in general the yields'oi product are much higher than by older methods andin some cases products are obtainable-which havebeen inaccessible using the older methods. It' is a further object of my invention'to provide certain new and useful dyes. Other objects will appear hereinafter. f

Distinctionjshould be drawn between the isolated use of theseorganic bases in small quantities as catalysts and their employment in the present instance in molecularly amounts. In the present casepa perusal of the examples will showthat the strong organic base is used to bind molecular proportions of acid, and

the two types of reaction are; therefore, entirely difierent. In the present invention the bases are not used as catalysts, but as preferred acid-binding agents.

The bases which I use, such as n-butylamine,

diethylamine, triethylamine, tri 'n-butylamine,

equivalent f 17 Claims. 01; 260-240) triethylamine is employed comparedwith when potassium hydroxide is employed. (See, for instance, my cop'eriding application Serial-No.

619,960, filed June?29,1932.) V

For instance, in the preparation-of 1,1-diethylb-cyanine iodide, a well known dye, the yield of unrecrystallized dye made using triethylamine amounts to as much as 80% of the theoretical, whereas the yield using caustic potash is deoided ly lower. In the preparation of 2,1"-diethylthiogv-cyanine' iodide, when triethylamine is used (2.1 mols. or base toeach 1 incl; of reacting salts) 'the yield obtained is around 90%. Using caustic potash under comparable conditions, the yield is appreciably'less, beingonly from -75%.

The corresponding selenium-containing dye may be similarly prepared.

q The results are stillmore striking with-2,1-

diethyl oxa-ip-cyanine iodide, anew die. This dye, which possesses the following structure,

7 Et is obtainable when caustic potash (2 mols.) is

allowed to react in absolute ethyl alcoholic so.-;

'lution on a hot mixture of l-methylbenzoxazole ethiodide and ,2-iodoquinoline ethiodide; The yield, however, in that case is small, being around 7%, and this remains roughly thesame when sodium ethylate is used in place of the caustic potash. However, when triethylamine is used the yield of unrecrystallized, but substantially pure dye, is around 67%.

Of the various methods suggested in my copending application (Serial No. 619,960) for the preparation of l ox dialkyl thi selen those methods in which triethylamine are used lazolo-xp-cyanine dyes,

usually better. i

Usually triethylamine, tri n-butylamine, ,s-diethylaminoethyl alcohol and such tertiary bases, give very high yields of the ip-cyanine dyes,and these bases are consequently preferred. Guani-= din carbonate is quite good "too for-the preparation of 2,1'-diethylthio-\p-cyanine iodide and of 1,1'-diethyl-i//-cyanine iodide, the yields being 85% and respectively, under the conditions employed. This reagent, however, 'is

less suitable for preparing 1,2' -diethyloxa--cy-- anine iodide. Piperidine too, while giving about a 40% yield of 2,1' diethylthio-ip-cyanine iodide," gives a small yield of 2,1'-diethyloxa--cyanine are preferred for the reason that the yields are iodide or of 1,l-diethyl-i//-cyanine iodide, but diethylamine gives an 80% yield of this first dye, a 20% yield of the second, and a 30% yield of the third dye.

The bases should be pure and anhydrous and the details of preparation of the dyes are furnished in the examples.

A further witness to the improvement in the method brought about by the use of triethylamine and the like in condensations ofthe ill-cyanine type is afforded by the reaction between 2-iodoquinoline alkyl iodide and a picoline alkyl iodide. When caustic potash is employed, a ip-cyanine cannot be isolated (Hamer and Kelly, J. C. S. 1931, 778, see also B. P. 369, 947, page 1, line 32) but when triethylamine is employed, the dye can readily be isolated,

Furthermore, it was not found possible (B. P. 369, 947, p. 1, 1.21) to prepare a cyanine dye of the constitution using potassium hydroxide, but using triethylamine this can be accomplished. Similarly it is also possible to prepare such rp-cyanine dyes as S\ Si CH and l CH CH=C u /CH=C H /N\ -0113 /N\ C-CH: R x I R p x i R R using 2-iodopyridine alkyl iodide and the appropriate quaternary salts of cyclic ammonium bases containing reactive methyl groups.

The dyes known as the isocyanines may also conveniently be prepared using the strong organic bases, and an example appears hereinafter showing how to prepare the dye 2,l-diethylselenoisocyanine iodide.

My new process is generally and particularly useful in preparing carbocyanine, dicarbocyanine and tricarbocyanine dyes, i. e. cyanine dyes containing a polymethenyl chain, e. g. a trimethenyl, a-pentamethenyl or a heptamethenyl chain.

The inability to obtain S-methyl substituted oxacarbocyanines has been recorded (Hamer, J. C. S. 1928, 3162), but these dyes can be obtained when thebase triethylamine is used in addition to the pyridine formerly used alone, showing clearly that the strong organic bases are by no means equivalent in action to pyridine.

The reaction may be expressed as follows R, R and R v are alkyl groups which may be similar or dissimilar. X is an acidic radical such as iodide or p-toluenesulfonate and A is the substituent grouping, usually alkyl, which it is desired to introduce into the 3-carb0n oxacarbocyanine chain. The compound A.C(OR )2(OR is an ortho-ester of a carboxylic acid which contains the substituent grouping A, such orthoesters having been described in some detail in my U. S. Patents Nos. 1,846,301, 2, 3 and 4. The reaction is conveniently performed in pyridine, the ortho-ester being employed in excess and the triethylamine, or equivalent base, also being employed in excess, if desired. The procedure is illustrated in the examples. A strong base, such as triethylamine, may also be similarly employed for the preparation of 8-substituted thioand seleno-carbocyanines.

It has also been found that very high yields of dicarbocyanine dyes containing a halogen substituent linked to the central carbon atom of the S-carbon chain may be obtained by the use of these strong organic bases. These dyes are described in J. C. S. 1932, 260 (cf. 13. P. 353, 889) and the present method is regarded as an improvement thereon. In general this reaction is carried out as follows. Two mols. of the alkyl quaternary salt of the cyclic ammonimum base containing a reactive methyl group are dissolved in hot absolute ethyl alcohol and the solution rapidly chilled in ice Water. If the quaternary salt separates out, as it usually does, the solution is stirred so as to produce small crystals. 1 mol. of a-bromo--anilino-acrolein anil hydrobromide (or a-chloro-fl-anilino-acrolein anil hydrochloride, or the like) is then added and the whole stirred. 2 mols. of base, such as piperidine, are then added with good stirring and the whole stood aside in the cold for a day. The dye is then isolated either by filtration, or precipitation with ether or double decomposition with an inorganic salt, such as potassium iodide, which gives a more sparingly soluble salt of the dye, or by a combination of these methods, they being all standard procedure. In most cases the yields are excellent. Variations of this procedure are also given in the appropriate examples.

Unsymmetrical dicarbocyanine dyes containing a halogen substituent attached to the central carbon atom of the 5-carbon chain have not hithereto been described. In order to prepare such dyes it is necessary to prepare an intermediate compound which contains the grouping and may be named 1-(4-acetanilido-3-bromo- 1,3-butadienyl)-benzothiazole ethiodide, and this compound dissolves with a pinkish orange solution in methyl alcohol.

COCH:

, compound and-quaternary salt The intermediate can be combined with=a secondfmolecule of ,alkyl quaternary salt, which may be the. same or dissimilar. In the first casethe symmetrical. dicarbocyanine is formed, and in the second case the dye is unsymmetrical.

step may in general be brought about by taking equimolecular' proportions of the intermediate in alcohol (methyl or ethyl) and adding a molecular ,proportioniof a strong .base such as piperidine. and allowing the whole to stand for some-hours. Thus, when 2,-methyl thiazoline methiodideis employed in conjunction with 1-(4-acentanilido- 3-bromo-'1,3-butadienyl) benzothiazole. ethiodide the, product is 3-methyl-2f-ethyl-8-bromothiazolinothiodicarbocyanine iodide.

The use of the strongorganic bases has also proved to be of great use in the preparation of the dyes known as the ,tricarbocyanines. For

instance, the. method described in B. P. 354, 826

is. much improved if one of the strong bases alreadymentioned is used in place of the sodium ethylate, there employed, and if the reactions areallowed to proceed at room temperature, or

lower, instead of boiling in alcoholic solution.

' Not only does this improvement result in greatly increased yields, but dyes of the 4,4''-tricarbocyanine class, which cannot be obtainedlby the method. of that patent become readily accessible by my novel method. These dyes have the general formula H R-N 0 -cH=cH-0H=cH-oH=cH 1,1-dialkyl-4,4-tticarbocyaninc salt dine. v i

Furthermore, the methodsof the original patents do .not appear to give the thiazolot'ricarbocyanines,"whilst they are readily obtainable using a myinvention. Thus 2-methylthiazole gives rise 3,3'-diethylthiazolotricarbocyanineiodide whilst 2,4-dimethylthiazole gives rise to asubstituted derivative as shown in the examples. v I 4 7 EXAMPLE 1 1,1'-dietii.;z1Z-.p-cy'am'neiodide 3 parts of quinaldine ethiodide (1 mol.) are heated-with 4.1 parts (1 mol.) of finely powdered 2-iodoquinoline ethiodide in 30 parts of boiling ethyl alcohol under reflux, and 2,1 (2.1 mols;, i. e. 5% excess) parts of triethylamine added down the condenser and the whole well shakenand refluxed for twenty minutes. The dye forms V rapidly, is filtered off when cold, washed with water, followed by a little alcohol and dried. The yield'of dye is about 3.7 parts which is about of the-theoretical. y

v When tri-n butyla'mine'is employed (3.7 parts, 2.1 mols.) the conditions being otherwise identical, the yield of dye is 76%. The use of guaniyield of about 80%".

dine carbonate (1.9 parts, 1.05 mol.) results in .a

,larly used results in a yield of carbonate (1.9 parts) gives a yield of 86% and vdiethylamine (1.55 parts) .gives a yield of 79%.

and are derived from quaternarysalts of lepi- EXAMPLE 2 2,1 diethul-orca-lp-cganine iodide 2.9 parts of l-methylbenzoxazole ethiodide and I 4.1 parts of 2-iodoquinoline ethiodide are-treated .in,20 parts of boiling absolute ethyl alcohol with 2.1 parts of triethylamine. The dye rapidly separates from the boiling solution and refluxing is continued for a further ten minutes. Thewashed 'dyeweighs 3 parts (67%) and crystallizes from ;methyl alcohol in orange' needles. Triethanolamine (3.15 parts) gives a yield of about 2 parts "of "dye and] 'p-diethylaminoethyl alcohol (2.5

:parts) gives about the same yield.

3.5 parts of l-methylbenzothiazole etho-p-toluenesulionate and 4.1 parts of 2-.iodoquinoline ethiodide are treated in 30 parts of boiling ethyl alcohol with, 2.1 parts of triethylamine and the mixture refluxed for twenty minutes. The dye separates outand after washing and drying is obtained in ayield of about 90%. p-diethylaminoethyl.alcohol (2.5 parts) simi- Guanidine EXAMPLE 4 7--methyl-1,z-dicthylthio-go-czlanine iodide 3.2 parts (1 mol.) 50f -,1-ethylbenzothiazole ethiodide amounts of 1-ethylbenzothiazole and ethyl iodide together in the usual way, and recrystallizing the product), 4.1 parts (1 mol.) of 2-iodoquinoline .ethiodide and ,18 parts of absolute ethyl alcohol 1 are refluxed together with 2 parts (2 mols.) of triethylamine for 15' minutes.

Crystals of the dye separate during .the'rea'ction and are filtered off ,on cooling andwashed free .from a soluble purplish impurity with a little acetone. The dye may be recrystallized from methyl alcohol and is obtained as small scarlet needles which give an" orange solution with thesolvent.

I 'ExAMPLn 5 v 2,1 diethylseleno-d-fillanine iodide (made by condensing equivalent v2 parts 1 mol.) of l-methylbenzoselenazole are sulfonate at 'C. for 30 hours. The product, a somewhat brownish ,viscous mass, is dissolved in' 16 parts of-hot absolute ethyl alcohol, 4.1 parts (1 mol.) of 2-iodoquinoline ethiodide added, the whole brought to boiling and 2.1 (2.1'mols.) parts of triethylamine added. The dye rapidly sepae rates but heating is continued for 20 minutes. On cooling the dye is removed, washed and puri fied by crystallization from ethyl alcohol in which it-givesan orange solution.v The dye forms scarlet needles with a blue reflex.

, v v EXAMPLE 6 1,3,3,1"-tetramethyZindo--cyanine iodide heated with 2 parts (1 mol.) of ethyl p-toluenev 65 3 parts ('1 mol.) of 2,3,3-trimethylindolenine methyl alcohol and formed reddish brown crystals. The yield of dye obtained is much higher than when potash is used.

1,1 '-dimetityl-5,6-benzopyrido-2g'-c'yanine iodide 2', 1-diethyZthio-2Q-pyridocyanine iodide 3.5 parts (1 moi.) of l-methylbenzothiazole etho-p-toluenesu1fonate and 3.6 parts (1 mol.) of 2-iodopyridine ethiodide are heated under reflux for 20 minutes with 12 parts of ethyl alcohol and 2.1 parts (2 mols.) of triethylamine. The dye rapidly separates from the boiling mixture.

.11; is collected when cold, washed and purified by recrystallization from methyl alcohol in which it gives ayellow orange solution. It forms long pale-yellow needles.

ExAMPLE 9 1,1 -dimethyl-'2,2 -py2id0cyanine iodide 2.4 parts (1 mol.) of u-l'J-lCOllllG methiodide, 3.5 parts (1 mol.) of 2-iodopyridine methiodide, 16 parts of absolute ethyl alcohol and 2.1 parts (2.1 mols.) of triethylamine are refluxed together. The dye begins to separate in glittering crystals from the boilingreaction mixture after 3 or 4 minutes, and refluxing is continued for 20 minutes. The dye is removed and is purified by washing with acetone followed by water, and is obtained in beautiful light brown platelets with a bright pale greenish reflex. It may be recrystallized from methyl alcohol when it is obtained in brown granular crystals with a green reflex. The color of the solu'tionis' golden-yellow.

' ExAMP'Ln 10 4,1-dimethyl 3 ethyithiazolo-Z-pyridocyanine iodide 2.7 parts (1 moi.) of 2,4-dimethylthiazole ethiodide, 3.5 parts (1 mol.) of 2-iodopyridine methiodide, 16 parts of absolute ethyl alcohol are brought to boiling, 2.1parts (2.1 mols.) of triethylamine added and the whole refluxed for 20 minutes. The dye rapidly separates from the boiling solution as a yellow-orange powder. It is removed, washed with acetone followed by water and may then be recrystallized from methyl alcohol in which it gives a yellow-orange solution. It separates as yellow needles or as orange needles with a bright greenish-yellow reflux, or as a mixture of the two forms. 1

EXAMPLE 1 1- hol, 3.5 g. (1 moi.) of Z-iodopyridine methiodide added, the whole boiled, 2.1 parts (2.1 mols.) oi

triethylamine added and-refluxed for 20 minutes. The dye rapidly separates from the boiling solu- EXAMPLE l2 2,1'-diethylselenoisocyanine iodide 2 parts (1 mol.) of l-methylbenzoselenazole were heated at 100 for a day or two with 2 parts (1 mol.) of ethyl p-toluenesulfonate The product was boiled with 20 parts of pyridine and 8.6 parts (3 mols. i. e. 200% excess) of quinoline ethiodide and 2 parts (2 mols. i. e. 100% excess) of triethyiamine, the'latter being added in portions over half a minute to the boiling pyridine solution of the two salts, the whole being then refluxed for 1 /2 minutes longer. The deep red solution was cooled and stirred with parts of ether and crystals separated. The residue was washed'with water followed by acetone. The dye (2 parts, about 38% yield) was obtained in the form of scarlet needles on recrystallizing it from methyl alcohol, the color of the solution being 7 orange-red.

EXAMPLE 13 2,1 '-diethylthioisocyanine iodide 3.05 parts (1 mol.) of l-methylbenzothiazole ethiodide, 5.7 parts (2 mol., 1. e. excess) of quinoline ethiodide, and 20 parts of pyridine were boiled together, 2.1 parts (2.1 mols., i, e. excess) of triethylamine added to the boiling solution and the whole refluxed for half an hour. On cooling the dye was precipitated from the reddish solution by adding 50 parts of ether and then washed with ether followed by acetone and then by water. The dye may be crystallized from methyl alcohol in which it forms a pinkish-orange solution.

EXAMPLE 14 7-methyZ-2,1'-diethylthioisocyanine iodide 3.2 parts (1 mol.) of l-ethylbenzothiazole ethiodide, 5.7 parts (2 mols., 100% excess) of quinoline ethiodide and 20 parts of pyridine are heated together, 2.1 parts (2.1 mols., 110% excess) of triethylamine added to the boiling solution and the whole refluxed for 30 minutes. he dye is precipitated by addin 100 parts of ether, the ethereal layer decanted and the residue washed successively with ether, water and acetone until crismson impurities are removed. The dye may be crystallized from methyl alcohol in which it dissolves with pinkish-orange solution.

H EXAMPLE 15 8methyl-2,2'-diethyloa2acarbccyanine iodide 2.9 parts (2 mols.) oi? l-methylbenzorzamle ethiodide were heated with 15 parts of pyridine, 3.25 parts of ethyl ortho-acetate (4 mols., i. e. 300% excess) and 1.1 parts of triethylamine (2.2 mols., i. e. excess) under reflux for three minutes. The dye is precipitated by adding ether to the cooled solution and is purified by washing with acetone followed by water and is recrystallizedfrom methyl alcohol when it is obtained in red prisms with a blue reflex." The solution is yel-' lowish orange.

EXAMPLE l6 2,2-dimethyl-8-ethylomcarbocyanine iodide 2.7 parts (2 mols.) of l-methylbenz'oxazoleis heated with 3.7 parts (2 mols.) of methyl p-toluenesulfonate at C. for some hours to prepare the quaternary salt. This salt is refluxed for seven minutes with 20 partsof pyridine, 7.05 1 parts (4 mols. i..e. 300% excess) of ethyl ortho propionate and 2.2 parts (2.2 mols., i. e. 'excess) of triethylamine. The dye is precipitated by the addition of ether, dissolved in methyla1-' cohol and precipitatedas the iodide by the addition of an aqueous solution of potassium iodide (5 g. in 30 cc. of water). The dye 'is collected, washed, and recrystallized from methyl alcohol in which itdissolves with an orange color. It is obtained as orange scarlet aggregates'of minute crystals or as much larger ones, some sides of which reflect blue light. 1

I ExAniPLE 1'7 v 9-br0mo -2',2'-diethylthiodicorbocyanine iodide This dye was obtained in high yield (94%) as follows: 6.1 parts (2111015.) of l-methylbenzothiazole ethiodide were boiled with 60 parts of ethylalcohol and the solution rapidly chilled with stirring. so as to get small crystals of the salt. 3.8

parts (1mo1.) of a-bromo-p-anilino acroleinlanil' I hydrobromide was then added, followed by 126 parts (2 mols.) 'of piperidine. The whole was well shaken'and kept at about 0 C. for 12 hours. The dye was then filtered off, washed with cold methyl alcohol and then hot methyl alcohol. It could be purified by recrystallization from methyl alco- I he] in which it gives a deep blue solution.

If the reaction was carried out in the hot,- the yield of dye was foundln'ot to be so high.

EXAMPLE 18 I bocyanine iodide a parts (2 mols.) of 1Fmethyl-u-naphthothiazole etho p-toluenesulfonate, 2.9 parts ('1 mol.) of ozbromo-fi-anilinoacrolein anil hydrobromide and 25 parts of absolute ethyl alcohol were well mixed together in'the cold and 1.3 parts (2 mols.) of piperidine added and the whole stood overnight without heating." The dye which separated was collected, dissolved in hot methyl 'alcoholand precipitated byadding excess of aqueous potassium iodide, and the same aqueous reagent was also added to the reaction liquor and a further" quantity or dye obtained. The combinedyields amounted to 5 parts (95% of. theory). The brassy-green powder so obtained could be crystallized from methyl alcohol and was obtained as chocolate brown crystals. dye is deepblue.

I EXAMPLE, 19 -11 b romo-1,1'-diethg Z 2,2(-dicarbocyanine br mid 6.9 parts (2 mols.); of quinaldine etho-'p-- toluenesulfonate, 3.8 parts (1 mol.) of ammoe-anilino acrolein anil hydrobromide and 20 parts of ethyl alcohol were mixed well together, chilled .in a freezing mixture and 1.7 parts (2 mols.) of

The solution of the piperidine added with good shaking and the whole kept at about 0 C. for 24 hours. Crystals separated during this period and were removed and dissolved in methyl alcohol and rep'recipitated.with' aqueous potassium, bromide. The

same reagent added to the reaction-liquor also I furnished more dye The'total yield of washed I dye was 4.7 parts (87%). The dye could be re-" 1 crystallized from methyl alcohol and was so obtained' in brassy-green'prisms which'gave a bluereen solution. v

EXAMPLEZO 11-bromo.-1,1-diethyl-4,4'-dicorbocyanine M bromide 10.3 parts (2 mols.) of Iepidine etho-p-toluene il sulfonate, 5.7 parts" (1 mol.) of' a-bI'Ol'ilOf-B-filflilil'lO the dried dye was parts (70%) EXAMPLE-21 3- methyl -2' -ethyl 8 bro'niothiazolinothiodicdrboe co -nine iodide The intermediate compound necessary for the preparation of this compound .was'made as fol- IOWS:,..:,. M

Equimolecular proportions ,of l-methylbenzothiazole etho p-toluenesulfonate and oz-bI'OIIlO-fianilinoacroleinanil hydrobromide are heated togetherin enough acetic'anhydride for complete solution for a short time, about one'half minute at a littlebelow the boiling point of the solvent. The solution-is then cooled somewhat and pouredinto, ether, theresidue washedwith more ether, -then dissolved inrnethylalcohol and stirred with aqueous potassium iodide in order to prepare the xiodide of the intermediatefi-Tl'ie residue was then filtered. off and. washed with more .water and crystallized from methyl alcohol. The compound forms brownish redcrystals witha coppery lustre and dissolvesv inmethyl alcohol witha pinkishorange coloration and mayv .very possibly have the structure.

Equimolecular;proportions of this compound. 1-(-acetanilido-3-bromo- 1.3 butadienyl) ben- '60 zothiazole' ethiodide, and of Z-methyl-thiazoline .HCBHE v methiodide are stirred in the cold withabsblute:

ethyl alcohol so as to make avery thin-paste and v 1 mol. oftriethylamine added. After some hours the product is collected, washed and recrystallized from-methyl alcohol when itis obtainedin dark blue lustrous needles which dissolve in the solvent with a purplish-blue- -color; I

This'dye-sen sitizes with a maximum at about 7}" t EXAMPLE "22 T? "2.27 dii yzthiomea boade e'zbd de fif 3.05pm. (2v mols.)" of 1-methylbenzothiazolelethiodide are dissolved in 40 parts of boiling absolute ethyl alcohol and the solution rapidlychilled with ice water to bring about crystallization with production of small crystals. 1.4 parts (1 mol.) of glutaconic aldehyde dianilide hydrochloride is then added, followed by 1 part (2 mols.) of triethylamine. The whole is kept near 0 C. for about 2 days with occasional shaking. The dye is then filtered off, washed with acetone followed by hot water and dried. The yield is around 70%.

Other bases such as n-butylamine, piperidine, tri-n-butylamine may be used, and all give good yields of the dye.

If 1-methyl-u-naphthothiazole ethiodide (2 mols.) is used in place of the quaternary salt used above, the dye obtained is 2,2'-diethyl-5,6,5,6- dibenzothiotricarbocyanine iodide which crystallizes in coppery crystals which give a green solution in alcohol.

EXAMPLE 23 1,1'-Methyl-2,2-tricarbocyanine iodide 6.9 parts (2 mols.) of quinaldine etho-ptoluenesulfonate, 2.8 parts (1 mol.) of glutaconic aldehyde dianilide hydrochloride and 22 parts of absolute ethylalcohol are mixed up together and the suspension chilled in a mixture of ice and concentrated hydrochloric acid. 1.7 parts (2 mols.) of piperidine are then added, with shaking and the whole kept at about 0 C. for a day. At the end of this time crystals had separated. These were dissolved in hot methyl alcohol, precipitated with aqueous potassium iodide and the reaction filtrate similarly treated. The total amount of crude dye was collected on a filter and washed with successive lots of hot acetone and finally hot-methyl alcohol to remove tars and bluish impurities. When the filtrate was a clear green color washing was discontinued. The yield of crude dye amounts to 2.6 parts (49%). On slow crystallization from methyl alcohol, magnificent brassy crystals were obtained. The yield of recrystallized material was 2.3 parts (43%).

EXAMPLE 24 2,2'diethylselenotricwrbooil/(mine bromide 2 parts (2 mols.) of l-methylbenzoselenazole are heated for a day with 2 parts (2 mols.) of ethyl p-toluenesulfonate at 100. The product is dissolved in 12 parts of absolute ethyl alcohol, the solution chilled in ice-water, 1.4 parts of glutaconic aldehyde dianalide hydrochloride added followed by 0.85 parts (2 mols.) of piperidine. The dye is rapidly formed and the whole is al lowed to stand for several hours at room temperature or somewhat lower. The dye is then precipitated with aqueous potassium bromide, collected, washed clean with water followed by acetone, and purified by recrystallization from methyl alcohol. It separates in beautiful green needles and gives a deep greenish blue solution.

EXAMPLE 25 1,1 '-diethyZ-4,4'-tricarbocyani1ue iodide 12 parts (2 mols.) of lepidine ethiodide were dissolved in 25 parts of absolute ethyl alcohol and the solution chilled in a freezing mixture with whole was stood aside in the ice box overnight. Next morning the muddy liquors were filtered off, the residue washed with acetone until most of the tarry impurities had disappeared, followed by water and then more acetone. The residue was next boiled with a small quantity of methyl alcohol, cooled and filtered, and this treatment repeated once or twice until the filtrate was a clear green color and the dye on the filter looked clean. It then consisted of coppery crysstals and gave a somewhat dull green solution. The dye could be successfully recrystallized from methyl alcohol, especially if the hot liquors were chilled so as to expose the dye to the action of the hot alocohol for as short a time as possible.

Lepidine methiodide, treated in the same fashion (llA parts are required) gave the dye 1,1'-dimethyl-4=,4-tricarbocyanine iodide. This was recrystallized from methyl alcohol and obtained as a dark brown crystalline powder, and the color of the solution was olive green. Lepidine alliodide similarly yielded l,l-diallyl-4,4- tricarbocyanine iodide, which was obtained in beautiful reddish coppery crystals. Triethylamine (2 mols.) could be substituted for the piperidine used in the above method.

EXAMPLE 26 3,3-diethylthiazolinotricarbocyanine iodide 5.1 parts (2 mols.) of Z-methylthiazoline were heated for 4 hours at 100 with 10 parts (2 mols.) of ethylp-toluenesulfonate. The yellowish viscous product was used without further purification, being dissolved in 25 parts of ethyl alcohol. the solution well chilled in a freezing mixture, 7 parts (1 mol.) of glutaconic aldehyde dianilide hydrochloride added to the solution followed by 4.3 parts (2 mols.) of piperidine. There was an instant very dark coloration and the whole was stood aside in the ice box overnight. Crystals of the p-toluenesulfonate of the dye separated on stirring in '70 parts of cold ether. The ethereal layer was poured off and the residue stirred with parts of acetone and filtered. The yield of air-dried dye is around 80%. The dye is then dissolved in hot methyl alcohol (25 parts) and precipitated by adding a solution of excess of potassium iodide (10 parts) in hot water (25 parts). The steely crystals could be crystallized from methyl alcohol in which they dissolved with a deep blue color.

1 EXAMPLE 27 3,3-diethylthiaeolotricarbocyanide iodide Z-methylthiazole etho-p-toluenesulfonate is prepared by heating 4 parts (2 mols.) oi 2-methylthiazole with 8 parts (2 mols.) of ethyl p-toluenesulfonate for 30 hours at 100. The product is dissolved in 20 parts of absolue ethyl alcohol, the solution chilled in ice water, 5.6 parts (1 mol.) of glutaconic aldehyde dianilide hydrochloride added and then 3.4 parts (2 mols.) of

piperidine. The whole is well shaken and stood in the icebox for about 120 hours. The deep blue liquid is then mixed with an excess of cold aqueous potassium iodide and the dye is precipitated, removed by filtration and washed with water. It is then treated with acetone, in which it dissolves readily, and on standing or on rubbing with a glass rod the dye separates out in beautiful greenish bronze crystals relatively insoluble in the solvent. These crystals are removed and may be recrystallized from methyl form a-"gfoupwhichin general comprises a'lialcohol, the color of the solution-being deepblue. The dye is then obtained in green needles, some facets of which reflect blue light and others brassy-green light.

EXAMPLE 28 3,4,3,4-tetramcthylthiazolotflcarboeydnine bromide 12 parts (2 mols.) of 2,4-dimethylthiazole metho-p-toluenesulfonate (made by condensing together equimolecular proportions of 2,4-dimethylthiazole and methyl p-toluenesulfonate) are dissolved in 24 parts of hot absolute ethyl alcohol, the solution rapidly chilled in a freezing mixture, 5.6 parts (1 mol.) of glutaconic aldehyde dianilide hydrochloride added, 3.4. parts (2 mols.) of piperidine, the whole well shaken,

' which may be recrystallized fromme'thyl alcohol,

or, the methyl alcoholic solution may be .treated with excess of aqueous potassium bromide, when the bromide of the dye separates out. This may be removed and recrystallized from methyl alcohol and it separates in green lustrous crystals" which give a deep blue solution.

From the foregoing description and numerous examples, it willbe apparent that the use of a strong organic base as a condensing agentfor the preparation ,of cyanine dyes has quite broad and general application. By its use, the yields of a large number of dyes is vastly improved and the synthesis of a number of dyes which have'heretofore defied preparation, is made possible. While many more examples could be given, the fore going are thought'to be sufiicient to teach the application of my method to cyanine dye reactionsin general, and it is a striking fact that "the simplest \//cyanine having the general formula IF -CH-Q I a R R I' and also the dye having the longest chain'of carbon atoms connecting the two nitrogenatoms yet discovered and having the general formula.

are both rendered accessible by this method;

While I have described the use of a considerable number of strong organic bases, it will be apparent to those skilled in the art that any strong organic base having similar properties may likewise be employed. In the claims appended hereto, when the term .stro'ngorganic base is used, it is not intendedfto include bases such as pyridine and quinoline, which'are of an Furthermore, I employ these bases in molecularly equivalent quantities,'rather aromatic type.

than in traces as catalysts. a

More specifically, it will be observed that thestrong organic bases which I prefer to employ,

' examples.

phatlc bases of the substituted ammonia type known as aliphatic amines. These amines may be primary, secondary or tertiary amines, the use of all of these types being illustrated in the It is also convenient to employ some of these basesin the form of their salts with weak acids, such as carbonic acid. There is a great variety of such bases available and it is not intended that the concept should be applied toorestrictively For instance, guanidine (in the form of its carbonate). is effective, while at the sametime it is not strictly regarded as an ali-' phatic amine.

The nomenclature of the new dyes described in this application is based upon that already in common use.

The numbering of the selenob-cyanine and seleno-isocyanine rings exactly follows that used in the cases of the relatedsulfur-containing dyes.

In the case of \p-cyanine and iso-cyanine dyes in which the hydrogen of the methenyl group is substituted by alkyl, such. as methyl, the position of. this groupis .s ecified by numbering the molecule, as shown.

and

where R and R' 'f are alkyl 'groupsand X is an acidic radical: and A is an alkyl group; preferablymethyl.v Y may be Spr Se. f m

may be considered" as a '1,1-dialkyl-2-pyrido-1,bcyanine iodide' or as 1,1 diaIkyI-Z-pyrido-Z cyanine iodide or' as 1,1'-dialkyl-5,6 (or 5 ,6)-

In the first of these names, the dy'eis regarded 'as a ,t-cyanine derived from quinoline and in the third name, the dye is regarded as a simple 2,2 '-pyride-cyanine with a benzene ring 'fused on to one of the pyridine rings. a a

Thedye f is named 1,1'-dialkyl-2,2 -pyridocyanine iodide, the'symbol (pseudo) being omitted since it is believed that the substitution of numbers leads to a clearer system of nomenclature.

The dye is named 2,1-dialkylthio-2'-pyridocyanine iodide, the numerals in the pyridine nucleus being primed (dashed) by analogy with the numerals in the quinoline nucleus of thiob-cyanine.

Similarly the dye below is named 3,1'-dialkylthiazolo-2'-pyridocyanine iodide, the use of the term "thiazolo" indicating the presence of the thiazole nucleus, which for simplicity retains its own (Ritcher) system of numbering. The selenium and oxygen compounds are precisely analogous.

The nomenclature of the 8-substituted oxacarbocyanines is based on that of the corresponding sulfur compounds, as described, for instance,

in my U. S. Patent No. 1,846,301.

The unsymmetrical dicarbocyanine is considered as a dicarbocyanine which contains a benzothiazole nucleus and a thiazoline nucleus. Presence of the former nucleus in a cyanine dye has for long been indicated by the use of the prefix thio, whilst thiazolino has been used (in my copending application No. 460,548) to indicate the presence of the thiazoline nucleus. Since both prefixes are required, they are chosen in alphabetical order and the dye is named a thiazolinothiodicarbocyanine. The numerals in the nucleus corresponding to the second prefix of the name, i. e. thio, are primed (dashed) and the carbon atoms of the chain are numbered out from the nucleus containing the plain numerals, as shown. The full name then becomes 3-methyl-2-ethyl-8-bromothiazolinothiodicarbocyanine iodide.

It is quite clear that in the pseudocyanines and isocyam'nes and unsymmetrical dicarbocyanines, etc. the alkyl groups may be like orunlike.

All of the dye syntheses mentioned in this application involve the use of one or two molecular proportions (to every molecular proportion of dye product, as shown in the equation of the reaction) of an alkyl quaternary salt of a nitrogen-containing cyclammonium base containing a reactive methyl (or mono-substituted methyl) group. In the claims such a salt is, for the sake of brevity defined as a cyclammonium alkyl quaternary salt.

It will be apparent to those skilled in the art that a great variety of alkyl quaternary salts of these heterocyclic ammonium bases containing reactive methyl, etc., groupings is available for the cyanine dye syntheses described in this application. The use of many of these sa s is indicated in the examples. Others were dealt with in my copending application No. 619,960. The parent bases such as l-methylbenzoxazole or l-methylbenzothiazole may be substituted in the available positions, but this does not affect or diminish the scope of this invention.

In the pseudocyanine condensation, the ter tiary bases give the best results and of these, triethylamine is usually the most reliable, although it is pointed out that some of the other bases also give good yields of dye. In some of the other condensations, the difierence is not so marked, and both piperidine, a secondary base, and 'triethylamine, a tertiary base for example, are valuable in the preparation of the diand tricarbocyanines. For any particular condensation, the most satisfactory base is soon determined by a series of comparative experiments.

All of the dyes herein described have the property to a greater or lesser degree of sensitizing photographic emulsions, such as gelatino-silverhalide emulsions, so as to make those emulsions responsive to the light in various portions of the spectrum. Such emulsions are described and claimed in applications of even date.

What I claim as my invention and desire to be secured by Letters Patent of the United States is:

1. In a process for the preparation of a cyanine dye containing a polymethenyl chain, said process being selected from the group consisting of a process wherein two molecular proportions of a cyclammonium quaternary salt substance containing a reactive alkyl group are condensed with one molecular proportion of other substance which provides a part of the polymethenyl chain and the elements of acid are eliminated from thecondensing substances, and a process wherein one molecular proportion of a cyclammonium quaternary salt substance containing a polymethenyl chain is condensed with one molecular proportion of a cyclammonium quaternary salt substance containing a reactive alkyl group and the elements of acid are eliminated from the condensing substances, the step which comprises employing an organic base whose dissociation constant is substantially greater than that of pyridine in quantity sufficient to bind the elements of acid eliminated.

2. In a process for the preparation of a cyanine dye containing a polymethenyl chain wherein two molecular proportions of a cyclammonium quaternary salt substance containing a reactive methyl group are condensed with one molecular proportion of other substance which provides a part of the polymethenyl chain and the elements of acid are eliminated from the condensing substances, the step which comprises employing a non-cyclic organic nitrogen base whose dissociation constant is substantially greater than that of pyridine in quantity suihcient to bind the elements of acid eliminated.

3. In a process for the preparation of a cyanine dye containing a polymethenyl chain wherein two molecular proportions of a cyclammonium quaternary salt substance containing a reactive methyl group are condensed with one molecular proportion of other substance which provides a part of the polymethenyl chain and the elements of acid are eliminated from the condensing substances, the step which comprises employing an aliphatic amine whose dissociation constant is quantity suificientto bind the elements of acid eliminated.

, 4. In a process for the preparation-of a cyanine dye containing a polymethenyl chain wherein two molecular proportions of a cyclammonium quaternary salt substance containing a reactive methyl group are condensed withone molecular proportion of other substance which provides a part oi": the polymethenyl chain and the elements of acid are eliminated from the condens-- ing substances, the step which comprises employing an alkyl amine whose dissociation constant is substantially greater than that of pyridine in quantity sufficient to bind the elements of acid eliminated.

5. In a process for the preparation of a cyanine dye containing a polymethenyl chain where.-

in two molecular proportions of a cyclammonium quaternary salt substancecontaining a reactive methyl group are condensed with one molecular proportion of other substance which provides a part of the polymethenyl chainand the elements of acid are eliminated from the condensing substances, the step which comprises employing a trialkyl amine whose dissociation constant is substantially greater than 1 that of pyridine in quantity sufllcient to bind the elements of acid eliminated.

6. In a process for the preparation of a cyanine dye containing a polymethenyl chain wherein two molecular proportions oi a cyclammonium quaternary salt substance containing a reactive methyl group are condensed with one molecular proportion of other substance which provides a part of the polymethenyl chain and the elements of acid are eliminated from the condensing substances, the step which comprises employing triethylamine in quantity sufilcient to bind the elements of acid eliminated.

7. In a process for the preparation of a cyanine dye containing a heptamethenyl, chain wherein two'molecular proportions of a cyclammonium quaternary salt substance containing a reactive methyl group are condensed with one molecular proportion of a condensation substance of glutaconic aldehyde and a primary aromatic amine and the elements of acid are eliminated from the condensing substances, the step Which comprises employing an organic base whose dissociation constant is substantially greater than that of pyridine in quantity sufiicientto bind the elements of acid eliminated. I l 8. In a processfor the preparation of a cyamonium quaternary salt substance containing a reactive methyl group are condensed with one molecular proportion of a glutaconic aldehyde dianilide hydrochloride substance and the elements of acid are eliminated from the condensing substances, the step which comprises employing piperidine in quantity sufficient to bind the elements of acid eliminated.

9. In a process for the preparation of a cyanine dye containing a heptamethenyl chain wherein two molecular proportions of a cyclammonium quaternary salt substance containing a reactive methyl group are condensed with one molecular proportion ofa glutaconic aldehyde dianilide hydrochloride substance and the elements of acid are eliminated from the condensing substances, the step which comprises employing trlethylamine in quantity sufficient to bind the elements of acid eliminated.

whose dissociation constant is 10. In a process for the preparation of a cyanine dye containing a heptamethenyl .chain wherein two molecular proportions of a thiazoline quaternary salt substance having a reactive methyl. group 'in the alpha position to the quinquevalent nitrogen atom are condensed with one molecular proportion of a glutaconic aldehyde dianilide substance and the elements'of acid are eliminated from the condensing substances, the step which comprises employing an organic base substantially greater than that of pyridine in quantity sufflv cientto bind the elements of acid eliminated.

I 11. In a process for the preparation of a cyanine dye containing a heptamethenyl chain wherein two molecular proportions of a benzoselenazoie quaternary salt substance having a reactive methyl group in the alpha position to thequevalent nitrogen atom are condensed with one molecular proportion of a glutaconic aldehyde dianilide substance and the elements of acid are eliminated from the condensing substances, the step which comprises employing an organic base whose dissociation constant is substantially greater than that of pyridine in quantity sufficient to bind the elementsof acid eliminated.

13. In a process for the preparation of a cyanine dye containing a heptamethenyl chain wherein two molecular proportions of a selenazole quaternary salt substance having a reactive methyl group in the alpha position to the quinquevalent nitrogen atom are condensed with one molecular proportion of a glutaconic aldehyde dianilide substance and the elements of acid are eliminated from the condensing substances, the step which comprises employing an organic base whose dissociation constant is substantially greaterthan that of pyridine in quantity sufficient to nine dye containing a heptamethenyl chain wherein two molecular proportions of a Z-methylthiazolinealkyl-p-toluenesulfonate sub s t an c e are condensed with one molecular proportion of a glutaconic aldehyde dianilide hydrochloride substance and the elements of acid are eliminated from the condensing substances, the step which comprises employing piperidine in quantity sulficient to bind the elements of acid eliminated.

15. In a process for the preparation of a cyanine dye containing a heptamethenyl chain wherein two molecular proportions of a 2-methylthiazoline-ethyl-p-toluenesulfonate substance are condensed with one molecular proportion of a glutaconic aldehyde dianilide hydrochloride substance and the elements of acid are eliminated from the condensing substances, the stepwhich comprises employing piperidine in quantity suincient to bind the elements of acid eliminated.

16. In a process-for the preparation of a cyanine dye containining a heptamethenyl chain wherein two molecular proportions of a l-methylbenzoselenazole alkyl-p-toluenesulfonate sulfistance are condensed with one molecular proportion of a glutaconic aldehyde dianilide hydrochloride substance and the elements of acid are eliminated from the condensing substances, the step which comprises employing piperidine in quantity sufiicient to bind the elements of acid eliminated.

17. In a process for the preparation of a cya- 10 nine dye containing a heptamethenyl chain wherein two molecular proportions of a l-methylbenzoselenazole ethyl-p-toluenesulfonate substance are condensed with one molecular proportion of a glutaconic aldehyde dianilide hydrochloride substance and the elements of acid are eliminated from the condensing substances, the step which comprises employing piperidine in quantity sufiicient to bind the elements of acid eliminated.

LESLIE G. S. BROOKER. 

